Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer

Persistent Link:
http://hdl.handle.net/10150/281796
Title:
Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer
Author:
Ward, Anna
Affiliation:
The University of Arizona College of Medicine - Phoenix
Issue Date:
Mar-2013
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the College of Medicine - Phoenix, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Collection Information:
This item is part of the College of Medicine - Phoenix Scholarly Projects 2013 collection. For more information, contact the Phoenix Biomedical Campus Library at pbc-library@email.arizona.edu.
Publisher:
The University of Arizona.
Abstract:
Cancer cells couple heightened lipogenesis with lipolysis to produce fatty acid networks that support malignancy. Monoacylglycerol lipase (MAGL) plays a principal role in this process by converting monoglycerides, including the endocannabinoid 2-arachidonoylglycerol (2-AG), to free fatty acids. Here, we show that MAGL is elevated in androgen-independent versus androgen-dependent human prostate cancer cell lines, and that pharmacological or RNA-interference disruption of this enzyme impairs prostate cancer aggressiveness. These effects were partially reversed by treatment with fatty acids or a cannabinoid receptor-1 (CB1) antagonist, and fully reversed by co-treatment with both agents. We further show that MAGL is part of a gene signature correlated with epithelial-to-mesenchymal transition and the stem-like properties of cancer cells, supporting a role for this enzyme in pro-tumorigenic metabolism that, for prostate cancer, involves the dual control of endocannabinoid and fatty acid pathways.
MeSH Subjects:
Prostatic Neoplasms; Monoacylglycerol Lipases
Description:
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.
Mentor:
Nomura, Daniel, PhD

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleMonoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate canceren_US
dc.contributor.authorWard, Annaen_US
dc.contributor.departmentThe University of Arizona College of Medicine - Phoenixen_US
dc.date.issued2013-03-
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the College of Medicine - Phoenix, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.collectioninformationThis item is part of the College of Medicine - Phoenix Scholarly Projects 2013 collection. For more information, contact the Phoenix Biomedical Campus Library at pbc-library@email.arizona.edu.en_US
dc.publisherThe University of Arizona.en_US
dc.description.abstractCancer cells couple heightened lipogenesis with lipolysis to produce fatty acid networks that support malignancy. Monoacylglycerol lipase (MAGL) plays a principal role in this process by converting monoglycerides, including the endocannabinoid 2-arachidonoylglycerol (2-AG), to free fatty acids. Here, we show that MAGL is elevated in androgen-independent versus androgen-dependent human prostate cancer cell lines, and that pharmacological or RNA-interference disruption of this enzyme impairs prostate cancer aggressiveness. These effects were partially reversed by treatment with fatty acids or a cannabinoid receptor-1 (CB1) antagonist, and fully reversed by co-treatment with both agents. We further show that MAGL is part of a gene signature correlated with epithelial-to-mesenchymal transition and the stem-like properties of cancer cells, supporting a role for this enzyme in pro-tumorigenic metabolism that, for prostate cancer, involves the dual control of endocannabinoid and fatty acid pathways.en_US
dc.typeThesisen_US
dc.subject.meshProstatic Neoplasmsen_US
dc.subject.meshMonoacylglycerol Lipasesen_US
dc.descriptionA Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.en_US
dc.contributor.mentorNomura, Daniel, PhDen_US
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